title: Targetability and biodistribution of radioiodinated hypericin: comparison between microdosing and carrier-added preparations.
abstract: OBJECTIVE
  To study the effect of co-injecting unlabelled hypericin (Hyp) on biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131 labelled hypericin ((123/131)I-Hyp), a necrosis avid agent for an anticancer radiotherapy.
  
  
  METHODS
  (123/131)I-Hyp was prepared with Iodogen as oxidant and formulated in 0.6 μg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol-400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture. Comparisons on biodistribution and necrosis uptake of NCA and CA(123)I-Hyp were conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour retention of CA(131)I-Hyp was assessed in severe combined immunodeficiency (SCID) mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg. Tissue-gamma counting (TGC), autoradiography and histology were performed.
  
  
  RESULTS
  TGC revealed no significant difference in organ biodistribution between RPLI-rats injected with NCA and CA(123)I-Hyp, except in intestines, liver, lungs and stomach (P<0.05). Both preparations showed hepatobiliary excretion since intestines and faeces retained the most radioactivity. NCA and CA(123)I-Hyp exhibited high avidity and selectivity for hepatic infarction. From the day after injection onward, CA(123)I-Hyp showed greater target accumulation (7-11%ID/g) than (123)I-Hyp alone (~4%ID/g; P<0.05). In RIF-1-SCID mice receiving CA(131)I-Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i. TGC findings were confirmed by histological and autoradiographic analysis.
  
  
  CONCLUSIONS
  The study demonstrated the co-injection of unlabelled Hyp affected necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term high retention into tumour necrosis characterizes the carrier-added (131)I-Hyp.
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Peter de
authors.initials: Pd
authors.lastname: Witte
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.affiliation: Radiology Section, University Hospitals, K.U. Leuven, Herestraat 49, B-3000, Leuven, Belgium. yicheng.ni@med.kuleuven.be.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D010569:Perylene; C004965:hypericin